Conventionally, an amide compound has been industrially produced by hydrating the corresponding nitrile compound using a reduced state copper as a catalyst. Recently, however, instead of the copper catalyst, a method using a microorganism enzyme as a catalyst has been developed, and such method is partially practiced now.
In an enzyme method, reaction conditions are gentle, and substantially no by-products are produced. Thus, such method can be effected according to an extremely simple process. Therefore, the enzyme method is considered to be effective as an industrial production method. Heretofore, many microorganisms have been found, which have an ability of hydrolyzing a nitrile compound to form an amide compound.
As such microorganisms, for example, mention can be made of genus Bacillus, genus Bacteridium, genus Micrococcus and genus Brevibacterium (JP-B-62-21519, corresponding to U.S. Pat. No. 4,001,081) (the term "JP-B" as used herein means an "examined Japanese patent publication"); genus Corynebacterium and genus Nocardia (JP-B-56-17918, corresponding to U.S. Pat. No. 4,248,968); genus Pseudomonas (JP-B-59-37951, corresponding to U.S. Pat. No. 4,637,982); genus Rhodococcus and genus Microbacterium (JP-B-4-4873, corresponding to U.S. Pat. No. 5,179,014); species Rhodococcus rhodochrous (JP-B-6-55148, corresponding to U.S. Pat. No. 5,334,519); and genus Rhodococcus strain (JP-B-7-40948, corresponding to U.S. Pat. No. 5,200,331).
While, in order to improve enzymatic activity and to suppress the decrease of enzymatic activity (deactivation) during a reaction, conventionally, various investigations have been conducted, which are as follows: a method wherein a reaction is effected at a low temperature of freezing point to 15.degree. C. (JP-B-56-38118, corresponding to U.S. Pat. No. 4,248,968), a method wherein a substrate having a low concentration is continuously fed through plural feed openings (JP-B-57-1234, corresponding to U.S. Pat. No. 4,248,968), a method wherein a microorganism or the treated product thereof is treated with an organic solvent (JP-A-5-308980) (the term "JP-A" as used herein means an "unexamined published Japanese patent application"), a method wherein a reaction is effected in the presence of a higher unsaturated fatty acid (JP-A-7-265090), a method wherein a microorganism cell is treated by crosslinking with, for example, glutaric aldehyde (JP-A-7-265091 and 8-154691), etc.
Under the above-described circumstances, the present inventors have conducted various investigations regarding the improvement of the production of an amide compound according to an enzymatic method. As the result, it was found that deactivation with time during a reaction, which could not be overcome by a conventional method, was caused. It is natural that the greater this deactivation is, the more an enzyme is required for the reaction. Accordingly, the settlement of this problem is extremely important, especially, in industrial-scale production.